Clinical and Imaging Features Associated With Fast Infarct Growth During Interhospital Transfers of Patients With Large Vessel Occlusions

Abstract

Background and objectives: Acute ischemic stroke patients with a large vessel occlusion (LVO) who present to a primary stroke center (PSC) often require transfer to a comprehensive stroke center (CSC) for thrombectomy. Not much is known about specific characteristics at the PSC that are associated with infarct growth during transfer. Gaining more insight into these features could aid future trials with cytoprotective agents targeted at slowing infarct growth. We aimed to identify baseline clinical and imaging characteristics that are associated with fast infarct growth rate (IGR) during interhospital transfer.

Methods: We included patients from the CT Perfusion to Predict Response to Recanalization in Ischemic Stroke Project, a prospective multicenter study. Patients with an anterior circulation LVO who were transferred from a PSC to a CSC for consideration of thrombectomy were eligible if imaging criteria were fulfilled. A CT perfusion (CTP) needed to be obtained at the PSC followed by an MRI at the CSC, before consideration of thrombectomy. The interhospital IGR was defined as the difference between the infarct volumes on MRI and CTP, divided by the time between the scans. Multivariable logistic regression was used to determine characteristics associated with fast IGR (≥5 mL/h).

Results: A total of 183 patients with a median age of 74 years (interquartile range 61-82), of whom 99 (54%) were male and 82 (45%) were fast progressors, were included. At baseline, fast progressors had a higher NIH Stroke Scale score (median 16 vs 13), lower cerebral blood volume index (median 0.80 vs 0.89), more commonly poor collaterals on CT angiography (35% vs 13%), higher hypoperfusion intensity ratios (HIRs) (median 0.51 vs 0.34), and larger core volumes (median 11.80 mL vs 0.00 mL). In multivariable analysis, higher HIR (adjusted odds ratio [aOR] for every 0.10 increase 1.32 [95% CI 1.10-1.59]) and larger core volume (aOR for every 10 mL increase 1.54 [95% CI 1.20-2.11]) remained independently associated with fast IGR.

Discussion: Fast infarct growth during interhospital transfer of acute stroke patients is associated with imaging markers of poor collaterals on baseline imaging. These markers are promising targets for patient selection in cytoprotective trials aimed at reducing interhospital infarct growth.

Figure 1. Relationship Between HIR and Core Volume With Interhospital Infarct Growth Rate (on a log10 Scale)

Among the group of patients with an HIR ≥0.40, 58% exhibited fast progression, whereas for a threshold of 0.50 and 0.60, this percentage increased to 67% and 76%, respectively. For core volume, a threshold of 2.5 mL results in 62% of patients with fast progression, for 7.5 mL 67% and for 15 mL 76%. HIR = hypoperfusion intensity ratio.

Figure 2. Association Between the Relevant Clinical and Imaging Parameters at the PSC and Fast IGR (on a log10 Scale)

NIHSS, HIR, core volume, and CBV index are dichotomized at the most optimal threshold for fast IGR prediction, according to the Youden index. The distribution of patients for every parameter: NIHSS (<14, n = 45; ≥14, n = 133), HIR (<0.50, n = 119; ≥0.50; n = 64), core volume (<7.5 mL, n = 104; ≥7.5 mL, n = 79), CBV index (≥0.85, n = 97; <0.85, n = 86), CTA collateral score (good, n = 141; poor, n = 41). For the patients with a core volume ≥7.5 mL, 67% will experience fast progression, for HIR ≥50, 67%, for NIHSS ≥14, 51%, for CBV index <0.85, 63% and 68% for poor collaterals on CTA. CBV = cerebral blood volume; CTA = CT angiography; HIR = hypoperfusion intensity ratio; IGR = infarct growth rate; NIHSS = NIH Stroke Scale.

Figure 3. Example of a Patient With Slow and Fast Interhospital Progression With Corresponding Imaging Characteristics

Patient 1: presented with a right M1 occlusion. At the referral hospital, CT perfusion showed a core volume of 0 mL with an HIR of 0.14. The collaterals on CT angiography were scored as “good.” At arrival at the comprehensive stroke center, after an interscan time of 222 minutes, core volume on MRI DWI was 2 mL, meaning an IGR of 0.6 mL/h. At 90 days mRS was 1. Patient 2: presented with a right M1 occlusion. At the referral hospital, CT perfusion showed a core volume of 21 mL with an HIR of 0.56. The collaterals on CT angiography were scored as “poor.” At arrival at the comprehensive stroke center, after an interscan time of 132 minutes, core volume on MRI DWI was 100 mL, meaning an IGR of 36 mL/h. At 90 days mRS was 6. CTA = CT angiography; CTP = CT perfusion; DWI = diffusion-weighted imaging; HIR = hypoperfusion intensity ratio; mRS = modified Rankin Scale; rCBF = relative cerebral blood flow.

Figure 4. 90-Day mRS Scores in Fast and Slow Interhospital Progressors

The difference between the slow progressors (<5 mL/h) and the fast progressors (≥5 mL/h) in the overall distribution of scores was statistically significant (shift analysis, adjusted common odds ratio for improvement of 1 point on the mRS, 2.35; 95% CI 1.28–4.31). mRS score at 90 days was not available for 19 patients (10 slow progressors and 9 fast progressors). mRS = modified Rankin Scale.